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University of Colorado Denver

Head & Neck Cancer Research Program at the University of Colorado Denver School of Medicine
 

Faculty Listing

Summary of Research Interests


 

molecular and cellular
mechanisms of HNC
Head and neck cancer stem cells HNC prevention MicroRNA HNC pathology/ detection

Xiao-Jing Wang
Lynn Heasley
Mary Reyland
Dennis Roop
Peter Koch
Bryan Haugen
David Norris

Dohun Pyeon
Cheng-Jun Hu

 

Qinghong Zhang
Steve Anderson
Douglas Graham
Robert Sclafani
Rebecca Schweppe
Andrew Thorburn
Raphael Nemenoff
Linda Barlow
Shi-Long Lu
Stephen Malkoski

 

Dennis Roop
Xiao-Jing Wang
Josef Refaeli
Antonio Jimeno
Cheng-Jun Hu
Rajesh Agarwal
Robert Sclafani
Madeline Kane
York Miller
David Raben
Xiao-Jing Wang
Qinghong Zhang
Barbara Frederick

 

Robert Greer
Marileila Garcia
John Song

 

Bioinfomatics
of HNC
Targeted HNC therapy
Aik Choon Tan Madeline Kane
David Raben
Bryan Haugen
Antonio Jimeno

  

Rajesh Agarwal, Ph.D.,  Professor, Department of Pharmaceutical Sciences
Dr. Agarwal’s laboratory studies methods to prevent cancer through the use of dietary and synthetic agents using cellular, biochemical and molecular mechanisms. They evaluate the cancer chemopreventive potential of dietary constituents employing several long-term animal tumor bioassay protocols, and short-term animal and cell culture assays.  Models include skin, prostate, breast, lung, colon, bladder.  They study mechanisms of cancer prevention using oncogenes and suppressor genes, for example, ras oncoprotein p21 processing enzyme farnesyltransferase, cell cycle modulation, p53, cyclins, cyclin dependent kinases, cyclin dependent kinase inhibitors (Cip 1/p21, Kip1/p27), apoptosis, and mitogenic and anti-apoptotic signaling pathways.  Further, the lab also studies photodynamic therapy, both in vivo and in vitro mechanisms of photodynamic effect of photosensitizers, specifically phthalocyanines, and evaluation of PDT effect of phthalocyanines in murine skin tumor models.   More on Dr. Agarwal TOP

 

Steven Anderson, Ph.D., Professor Department of Pathology, James C Todd Chair of Experimental Pathology, Vice Chair of Research
Dr. Anderson is interested in the role of Akt in mammary gland development and tumorigenesis.  In addition to suppressing apoptosis, Akt may be important in regulating glucose transport, and the physiology of mammary epithelial cells during lactation.  Akt accelerates tumor formation via the ErbB2/Neu oncogene in transgenic mouse models, and may be important in altering the physiology of these cells.  The Anderson laboratory has recently published studies indicated that IGF1 can be used to prevent radiation–induced damage to the salivary glands.  Irradiation of the head and neck region is a primary means for treatment of head and neck tumors and some 40,000 Americans each year suffer from xerostomia secondary to this treatment.  The results may provide a new therapeutic regime for prevention of xerostomia.  The Anderson lab is also involved in studies using MMTV transgenic mice as models for salivary gland tumorigenesis focusing upon ErbB2/HER2 and Akt.  More on Dr. Anderson TOP

Linda A Barlow, Ph.D., Associate Professor, Department of Cell and Developmental Biology, Charles C. Gates Regenerative Medicine and Stem Cell Biology Program, and the Rocky Mountain Taste and Smell Center
The aim of the Barlow lab is to elucidate the cellular and molecular mechanisms which govern assembly of a functional taste system by the time newborns begin to feed, as well as which regulate the continual renewal of taste bud cells throughout adult life.  Much of the work focuses on the development and postnatal maintenance of taste buds. Taste buds are unique among sensory organs because they possess characteristics of both neurons (electrical excitable, release neurotransmitter) and epithelia (continual cell renewal).  In fact, the lab has have begun to encounter parallels with skin in our studies of taste epithelium. Further, the lab is developing a murine model for radiotherapy induced taste loss.  Radio and chemotherapies for head and neck cancers often result in an unintended taste loss, leading to an additional loss in quality of life.  Currently the lab is investigating the impact of head irradiation on cell cycle kinetics and taste cell progenitors in the lingual epithelium of wild type and mutant mice, as well as developing a behavioral assay to detect loss in taste sensitivity in irradiated mice.   More on Dr. Barlow  TOP

Barbara Frederick, M.D., Assistant Professor, Dept. of Radiation Oncology   Dr. Frederick is interested in developing biomarkers to predict patient response to targeting agents and radiation therap; sequencing combinations of targeted agents and radiation; induction of miRNAs by radiation; and the epigenetic events that drive tumor progression.   TOP

Marileila Varella-Garcia, Ph.D.,  Professor, Dept of Medicine, Medical Oncology Division, Dept of Pathology
Dr. Varella-Garcia has research interests in the development and validation of biomarkers for early detection and monitoring of recurrence in human neoplasias and patient stratification for therapy.  Dr. Varella Garcia focuses on translational cancer research using cytogenetics technology. Examples of scientific accomplishments in her laboratory are fluorescence in situ hybridization (FISH)–based assays developed for detection of chromosomal imbalance in interphase cells that diagnose sub-clinical tumorigenesis in head and neck and lung cancers. Aiming to better support molecular targeted therapies and efficiently identify patients likely to benefit from these therapies, her laboratory investigates genomic imbalances in metabolic pathways important in oncogenesis using FISH technology. Molecules addressed in these studies are HER-2/neu, EGFR and cyclin D1 (CCND1). Ongoing studies also address IGF1R, FGFR, MET, BRAF, and the gene fusions involving TMPRSS2 in prostate and ALK in NSCLC. Recently, her laboratory developed a FISH scoring system (EGFR-FISH) that identifies NSCLC patients more likely or unlikely to benefit from therapy with EGFR tyrosine kinase inhibitors. Dr. Varella Garcia is also the director for the Cancer Center Cytogenetics Core responsible to make standard and advanced cytogenetics technology accessible to Cancer Center investigators and their laboratories and to provide a source of expertise on experimental design, data analyses and interpretation.  More on Dr. Varella-Garcia  TOP

Douglas Graham, M.D., Ph.D., Assistant Professor, School of Pediatrics, Department of Immunology
Dr. Graham’s laboratory studies how abnormal activation of the Mer and Axl receptor tyrosine kinases leads to abnormal anti-apoptotic and proliferative signaling in cancer cells.  Using xenograft and transgenic mouse models, we are investigating in vivo the cooperative role of the Mer and Axl tyrosine kinases in oncogenesis. The animal models are also being used to test specific Mer and Axl inhibitors as a novel means of biologically targeted cancer therapy.  In collaboration with Lynn Heasley, the Graham lab has found Mer, Axl, and Tyro-3 receptor tyrosine kinases to be significantly upregulated in head and neck cancer cell lines.   Previous work in other solid tumors (glioblastoma, non-small cell lung cancer) has demonstrated that these tyrosine kinases provide a pro-survival response and mediate resistance to chemotherapy.  The lab is investigating whether Mer, Axl, and Tyro-3 may, in a similar manner, be novel targets for biologically targeted therapy in head and neck cancer.  More on Dr. Graham  TOP

Robert Greer, D.D.S., Sc.D. Professor, School of Dental Medicine, Oral and Maxillofacial Pathology, School of Medicine, Pathology
Dr. Greer’s research group which includes Dr. Sherif Said, Dr. Arlen Meyers, and Dr. Ken Shroyer, has largely been interested in the role of the human papillomavirus and cancer of the oral cavity.  We have worked on the relationship between human papillomavirus infection in the cervix and the oral cavity for some twenty-odd years.  Recently the lab has been very interested in the expression of p16 protein in precancers and cancers of the oral cavity.  The lab ran the largest known clinical trial involving the use of ketorolac as a preventative rinse for oral pharyngeal precancers in association with Dr. Jim Mulshine at the National Cancer Institute. On a clinical level we are still investigating the role of chemo-preventative agents in oral cancer.   More on Dr. Greer  TOP

Bryan Haugen, M.D., Professor, Department of Medicine, Endocrinology Division
Dr. Haugen is studying novel therapeutic pathways in advanced thyroid cancer using in vitro and in vivo models as well as human clinical trials.  Pathways under study include nuclear hormone receptor signaling (PPAR, RXR, VDR), MAPK signaling (RET-Ras-BRAF-MEK, NFΚβ) and the role of β-catenin in cancer progression.  His laboratory is using pharmacologic (novel pathway inhibitors and agonists) as well as genetic (overexpression of specific targets, gene silencing) to dissect signaling pathways in advanced thyroid cancer.  More on Dr. Haugen  TOP

Lynn Heasley, Ph.D., Professor School of Pharmacy, Department of Craniofacial Biology, School of Medicine, Department of Pharmacology
Dr. Heasley’s laboratory is interested in signal transduction pathways that negatively and positively control cellular transformation. The primary focus is on the c-Jun N-terminal kinases (JNKs), which appear to function either as tumor suppressors or pro-transforming signals in a context-dependent manner.  Another project in the lab is elucidation of autocrine growth factor signaling pathways in cancer cells. Recent studies have unveiled a dominant role for FGF and FGF receptors in both lung cancer and head and neck cancer cell lines.   More on Dr. Heasley  TOP

Cheng-Jun Hu, Ph.D., Assistant Professor, School of Dentistry, Department of Craniofacial Biology, School of Medicine, Department of Pathology
One common phenomenon of the solid tumors is hypoxic microenvironment.  Transcription factors, hypoxia-inducible factor (HIF)-1α and HIF-2α are active only under hypoxic conditions and promote tumor growth and progression by activating tumor angiogenesis, anaerobic metabolism, and metastasis. The lab is interested in the individual role of HIF-1α and HIF-2α in cancer progression and the transcriptional co-factors that regulate HIF transcriptional activity.  More on Dr. Hu  TOP

Antonio Jimeno, M.D., Ph.D., Assistant Professor School of Medicine, Department of Medicine, Medical Oncology
Dr. Jimeno’s research is focused on new drug and biomarker development in Head and Neck and Upper Gastrointestinal cancers. As a physician/scientist, Dr. Jimeno’s aim is to bridge the lab and the clinic by 1) developing direct patient xenograft models of head and neck and other cancers to generate better cancer models and as a platform to study cancer stem cells, 2) conducting preclinical tests of targeted agents against de-regulated pathways and cancer stem cells, and 3) devising ways to integrate that knowledge into clinical trials to individualize anti-cancer therapy.  More on Dr. Jimeno  TOP

Madeline Kane, M.D., Professor School of Medicine, Department of Medicine, Medical Oncology
Dr. Kane’s focus is on clinical studies in Head and Neck, GI and Thyroid cancer research. A priority in her career continues to be ensuring medical students, residents, fellows, and junior faculty members identify their career focus and successfully pursue it through cancer research training grants.  She is the Medical Director of the UCCC Clinical Investigations Core (CIC) where she oversees all clinical research studies and the management of its day-to-day activities.  More about Dr. Kane  TOP

Peter. J. Koch, Ph.D., Associate Professor, School of Medicine, Department of Dermatology, Director Transgenic and Gene Targeting Core
The goal of Dr. Koch’s laboratory is to understand the function of individual desmosomal proteins in pre- and post-natal development as well as in diseases, in particular head and neck cancer. To that end, the lab generates and analyzes genetically engineered mouse lines with mutations in desmosomal genes (knock out, knock in, conventional and BAC transgenics) and determines their susceptibility to cancer induction and progression. A key experimental approach to test the role of desmosomal genes in this process is to generate mice that co-express activated RAS oncogene as well as mutant versions of desmosomal proteins in the oral cavity.  For example, the lab is investigating the role of the armadillo protein plakophilin 3 (Pkp3) in oral cancer. To that end, we recently generated Pkp3 null mice with inducible expression of an activated Ras oncogene in the oral cavity.  More on Dr. Koch  TOP

Shi-Long Lu, M.D., Ph.D., Assistant Professor, School of Medicine, Department of Otolaryngology

Dr. Lu's research is focused on squamous cell carcinomas (SCC) from the oral cavity and esophagus using both human cancer tissues and genetically engineered mouse models.  A major goal is to understand the role of the PI3K/PTEN/AKT signalling pathway in the initiation, progression and metastasis of oral SCC and esophageal SCC. More on Dr. Lu

Stephen Malkoski, M.D., Ph.D.,  Assistant Professor, School of Medicine, Department of Medicine, Division of Pulmonary Sciences and Critical Care
The Malkoski lab focuses on how defects in TGFβ signaling promote the development and growth of lung cancer.   The lab evaluates the consequences of defective TGFβ signaling using human lung cancer samples, cell culture systems, and mouse models.   TOP

York Miller, M.D.,  Professor of Medicine, School of Medicine, Department of Medicine, Division of Pulmonary Sciences and Critical Care; Thomas L. Petty Chair in Lung Research)
The Miller lab is studying murine models of lung carcinogenesis and translating these to clinical trial of chemoprevention.    The lab uses genetically modified mice to determine mechanisms of susceptibility and resistance to lung carcinogenesis.  The role of hypoxia in lung cancer promotion is an additional area of research. The Miller lab also works on the discovery and validation of biomarkers of lung cancer risk in sputum, blood and lung tissue.  Further, the lab is assessing the response of these biomarkers to chemoprevention agents in phase II trials. More on Dr. Miller  TOP

Raphael A. Nemenoff, Ph.D., Professor of Medicine
The focus of Dr. Nemonoff’s lab is examining the molecular events mediating initiation and progression of lung cancer.  Specifically, we are studying two interacting pathways that contribute to this process:  production of eicosanoids, which are bioactive signaling lipids, and nuclear receptors of the peroxisome proliferator-activated receptor family.  Our studies examine these pathways in lung cancer cell lines, co-culture of cancer cells with stromal cells, and in mouse models.   More on Dr. Nemenoff  TOP

David Norris, M.D., Professor and Chairman School of Medicine, Department of Dermatology
Director of NIAMS Training Grant in Immunodermatology

Dr. Norris conducts research in immune mechanisms of immunologic diseases such as photosensitive lupus, vitiligo and alopecia areata has developed into studies of keratinocytes and melanocytes as targets of immunologic damage and participants in their own death.  The goal of Dr. Norris’ research programs is to understand the mechanisms that control programmed cell death in the skin, and how these mechanisms are altered in disease.  His research team is investigating the anti-apoptotic defenses in normal skin and in skin disorders caused by inflammatory or immunologic tissue reactions. In addition, his team is studying mechanisms of anti-apoptotic defenses of cancers in the skin including melanoma and basal cell carcinoma.   Dr. Norris has a long-standing interest in cell death in autoimmune diseases such as photosensitive lupus, vitiligo and alopecia areata.  He has also investigated how inflammation in the skin can be promoted by bacterial products such as bacterial superantigens. His most recent research efforts have focused on modulating anti-apoptotic defenses in melanocytes and melanoma.  Dr. Norris’ research interest in apoptosis and in discovering ways to reverse anti-apoptotic defenses will be amenable to collaborations with other members of the Head and Neck Cancer Research program.  More on Dr. Norris  TOP

Dohun Pyeon, PhD, Assistant Professor, Department of Microbiology

With the rising of HPV-related HNC, Dr. Pyeon, an expert of HPV pathogenesis, brings a unique expertise to our training program.  The Pyeon lab studies human papillomaviruses, with a focus on how HPR interacts with the host factors to establish persistent infection and develop invasive cancers. To better understand underlying mechanisms and genetic determinants of HNC progression, his lab is 1) identifying host factors/pathways that contribute to cancer progression and 2) developing key targets for treatment of HPV-associated cancers and novel biomarkers for diagnosis and prognosis. In global gene expression analyses of human oral and cervical tissue specimens, Dr. Dohun Pyeon found that several chemokines are specifically downregulated in HPV-positive cancers. More on Dr. Pyeon TOP
 

David Raben, M.D., Professor, School of Medicine, Department of Radiation Oncology
David Raben is a professor of Radiation Oncology and has worked primarily on new drugs that interfere with specific parts of the cancer cell signaling process to enhance radiation therapy. His focus has been on patients with locally advanced head and neck cancer, lung cancer and pancreatic cancer. He is a principal investigator on multiple clinical trials that have brought some of these new drugs into the clinical arena on both a local and national level.   More on Dr. Raben  TOP

Josef Refaeli, Ph.D, Associate Professor, Department of Dermatology, Charles C. Gates Medicine and Stem Cell Biology Program
Dr. Refaeli’s lab is interested in defining molecular mechanisms involved in the initiation, establishment and maintenance of lymphoid tumors.  The work is based on the hypothesis that lymphoid neoplasms arise as a result of the dysregulation of signals normally controlling lymphoid function and homeostasis.  There are three main areas of interest 1) identifying the nature and identity of antigen-receptor derived signals that can cooperate with dysregulated oncogenes; 2) determining the mechanisms by which the proto-oncogne MYC is able to regulate lymphoid tolerance; and 3) studying the contribution of MYC to the regulation of self-renewal, proliferation and differentiation of long-term hematopoietic stem cells.  More on Dr. Refaeli  TOP

Mary Reyland, Ph.D., Professor School of Dentistry, Department of Craniofacial Biology
The Reyland laboratory is interested in how specific members of the protein kinase C (PKC) family function to modulate apoptosis. Using salivary epithelial cells either in culture, or derived from genetically modified mice that have specific defects in protein kinase C directed signal transduction, our goal is to identify nuclear phosphorylation targets of PKCδ and to understand the mechanism by which PKCδ regulates the apoptotic pathway. Studies are also underway to understand the molecular mechanisms by which PKCδ is activated during apoptosis and to identify “downstream” pathways through which protein kinase C regulates apoptotic-specific gene expression.  More on Dr. Reyland  TOP

Dennis Roop, Ph.D., Professor School of Medicine, Department of Dermatology, Director, Charles C. Gates Medicine and Stem Cell Biology Program
Studies from the Roop laboratory have shown the accumulation of genetic defects in epidermal stem cells eventually results in tumor formation and we have recently discovered that skin tumors themselves are maintained by defective stem cells, referred to as cancer stem cells.  The lab’s current research efforts are focused on isolating and characterizing cancer stem cells.  An improved understanding of cancer stem cells could result in the development of novel therapeutic strategies that specifically target cancer stem cells for destruction and prevent tumor recurrence.  More on Dr. Roop  TOP

Rebecca Schweppe, PhD, Assistant Professor, Department of Medicine, Division of Endocrinology

Dr. Schweppe’s research is directed toward identifying novel molecular targets relevant to papillary and anaplastic thyroid cancer (PTC and ATC), with the ultimate goal of advancing these studies into clinical trials for thyroid cancer patients who do not respond to standard therapies. She recently showed that FAK is overexpressed and phosphorylated in thyroid tumor samples, and that inhibition of the FAK-Src pathway blocks growth and invasion in cells with high phospho-FAK. She is developing new thyroid cancer cell lines, and characterizing pathways important in thyroid cancer; the goal is to apply global molecular and genomic approaches with novel computational analyses to the new and existing thyroid cancer cell lines to uncover pathways important in thyroid cancer development and progression. More on Dr. Schweppe TOP

 

R. A. Sclafani, Ph.D. Professor, Department of Biochemistry and Molecular Genetics; Interdepartmental Training Programs-Molecular Biology, Cancer Biology, Biomedical Sciences, Human Medical Genetics, MSTP
The main area of focus of the laboratory is the regulation of the G1 to S phase transition of the cell cycle in yeast and human cells, especially the processes of chromosomal DNA replication and mutagenesis. When these processes are altered, it results in mutations and aneuploidy, which lead to cancer. By studying these processes, we hope to provide important information for cancer patient diagnosis, prognosis and in design of therapies. More on Dr. Sclafani TOP

John Song, M.D. Associate Professor, School of Medicine, Department of Otolaryngology
Dr. Song is clinically based, with an emphasis on cranial base surgery, and actively pursuing new, innovative surgical techniques.   More on Dr. Song  TOP

Aik Choon Tan,  Ph.D., Assistant Professor, School of Medicine, Department of Medicine, Medical Oncology

The Tan lab is interested in using translational bioinformatics to better understand cancer.  Two areas are of particular interest; 1) identifying simplified gene signatures using machine learning processes, and 2) integrating muli-layer data sets (mRNA and miRNA expression, metabolomics, CGH, SNPs, and ChiP-seq) using pathway driven anaylses to devise pathways and identify hierarchial relationships between these layers. More on Dr. Tan

Andrew Thorburn, Ph.D., Professor School of Pharmacy, Department of Pharmacology
The Thorburn lab studies the mechanisms of cell death regulation during the development and treatment of cancer.  Projects in the lab focus on: 1. characterization of a novel apoptotic and autophagic cell death pathway that we think is one of the earliest cell death-related defects that arise during the development of epithelial cancers. 2. Analysis of the tumor cell killing by therapeutic antibodies that target death receptors.  3. Analysis of the mechanism of action of tumor-targeted bacterial toxins that are in clinical development for treating acute myeloid leukemia and brain tumors.   More on Dr. Thorburn TOP

Xiao-Jing Wang, M.D., Ph.D., Professor and Director Head and Neck Cancer Research Program, Departments of Pathology, Dermatology, and Otolaryngology
Dr. Wang’s laboratory has developed the first genetically engineered mouse model that develops HNSCC with full penetrance. These lesions mimic human HNSCC at genetic and pathology levels.  Research in the Wang laboratory includes: 1) Identification of biomarkers for diagnosis and therapy for human head and neck cancer, 2) Development of animal models for head and neck cancer, 3) Molecular mechanisms of head & neck cancer including the properties of cancer stem cells, transcriptional machinery and microRNA functions, and 4) Experimental therapeutics of head and neck cancer.  More on Dr. Wang   TOP

Qinghong Zhang, Ph.D., Assistant Professor, School of Medicine, Department of Dermatology
Transcriptional regulation governs a broad spectrum of cellular activities: cell cycle progression, cell migration, apoptosis, or metabolism. Dr. Zhang is interested in elucidating the molecular mechanisms underlying transcriptional regulation in response to physiological and pathological signals. Particularly, her research over the past decade has focused on CtBP, a transcriptional co-repressor, and has uncovered a unique function of this protein as a redox-sensor in transcription control. This function allows cells to couple the metabolic status with gene expression. Furthermore, CtBP is subjected to post-translation modifications in response to cellular stress, consequently, triggering apoptosis independent of p53. Both aspects of this research have important therapeutic implications in human diseases. The ultimate and long-term goal is to develop drugs against metabolic disorders and cancers based upon molecular details as revealed by basic research.   More on Dr. Zhang  TOP

Head & Neck Cancer Research Program

Pamela Garl, MS, MBA • Program Administrator
Phone: 303-724-6480 • Fax: 303-724-7430

Street Address: 12801 17th Avenue, RC1-North Room 5130 • Mailing Address: Campus Box 8104, Aurora, CO 80045

E:mail: Pamela.Garl@ucdenver.edu

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